Carboxylic acids are useful in several fields such as medical, industrial, nutritional and agricultural fields. The methods for preparation of carboxylic acids can be mainly classified into two types of reactions, oxidation and hydrolysis reactions.
(1) Oxidation Reactions:
(a) Oxidation of arene side-chains: Under strong oxidizing conditions such as hot acidic KMnO4, arenes with benzylic-H are oxidized to the aromatic carboxylic acid. The oxidized side-chain substituent can be primary or secondary alkyl, while tertiary alkyl are not oxidized because they lack a benzylic-H. U.S. Pat. No. 3,282,992 describes the oxidation of ethylbenzene with aqueous ammonium dichromate at 225-275° C. yielded benzoic acid with minor amount of acetophenone and benzamide. Oxidation of arenes with side-chains higher than a methyl group can be considered as cleavage oxidation.(b) Oxidation of primary alcohols: Primary alcohols can be oxidized to aldehydes or further to carboxylic acids. In aqueous media, the carboxylic acid is usually the major product when using reagents such as aqueous Cr (VI), chromic acid (H2CrO4), chromate salts (Na2CrO4), dichromate salts (K2Cr2O7), permanganate MnOt and Jones' reagent (CrO3/dil H2SO4/acetone). Anhydrous oxidants such as pyridinium chlorochromate (PCC) or pyridinium dichromate (PDC), which are used in dichloromethane, allow the oxidation to be stopped at the intermediate aldehyde. Secondary alcohols can be oxidized to ketones but no further, while tertiary alcohols cannot be oxidized since they have no carbinol C—H. For example, CrO3-catalyzed oxidation of primary alcohols to carboxylic acids proceeds with 1-2 mol % of CrO3 and 2.5 equivalents of H5IO6 in acetonitrile to give the corresponding carboxylic acids. Moreover, alcohols can be transferred into the corresponding carboxylic acids with aqueous 70% t-BuOOH in the presence of catalytic amounts of bismuth(III) oxide. By using Pd/C along with NaBH4 in aqueous EtOH or MeOH and either K2CO3 or KOH at ambient temperature, alcohols can be oxidized to their carboxyl counterpart. Catalytic oxidation of alcohols can be realized by using o-iodoxybenzoic acid (IBX) in the presence of oxone as a co-oxidant. Pyridinium chlorochromate (PCC) catalyzed (2 mol %) oxidation of primary alcohols and aldehydes using 2.2 equivalents and 1.1 equivalents of H5IO6 leads to the synthesis of carboxylic acids. Selective aerobic oxidations in ionic liquids convert various primary alcohols into their corresponding acids or aldehydes in good yields. For examples, see M. Zhao et al., Tetrahedron Lett. 1998, 39, 5323-5326; P. Malik et al., Synthesis 2010, 3736-3740; M. Hunsen, Synthesis 2005, 2487-2490.(c) Oxidation of aldehydes: Many of the stronger oxidizing agents, such as KMnO4 and Tollens' reagent (Ag2O; Ag+/NH4OH), can transform aldehydes into carboxylic acids. As an example, the oxidation of aldehydes to carboxylic acids can be realized utilizing oxone as an oxidant. In addition, carboxylic acids can be prepared from aldehydes using pyridinium chlorochromate (PCC) and H5IO6. Aromatic aldehydes can be oxidized to carboxylic acids using sodium perborate. Furthermore, permanganate can be applied as an oxidant in the transformation of aldehydes to carboxylic acids. For examples, see B. R. Travis et al., Org. Lett. 2003, 5, 1031-1034; A. McKillop et al., Tetrahedron 1989, 45, 3299-3306; J. Sedelmeyer et al., Org. Lett. 2010, 12, 3618-3621.(d) Oxidative cleavage reactions: (i) Oxidative cleavage of ketones: Haloform reaction (X2/NaOH, X=Cl, Br, I) has some synthetic utility in the oxidative demethylation of methyl ketones, if the other substituent on the carbonyl groups bears no enolizable α-protons. From an environmental point of view, the conversion of acetophenone to benzoic acid using sodium hypochlorite through haloform reaction is not suitable for industrial use due to the formation of chloroform as a side product. Homogeneous catalyst, such as 1,3-dinitrobenzene and nitric acid, can be used to oxidize acetophenone. However, nitric acid oxidation of acetophenone gives dibenzoylfurazan 2-oxide and benzoylformic acid in addition to benzoic acid. The liquid phase oxidation of acetophenone over rice husk silica vanadium catalyst leads to the products benzoic acid, 2-hydroxyacetophenone, phenol, acetic acid, and 3-hydroxyacetophenone. (S. Adam et al., Chin. J. Catal. 2012, 33, 518-522). Catalytic oxidation in vapour phase of acetophenone to benzoic acid over binary oxides V2O5—MoO3 catalyst resulting in the formation of maleic anhydride, benzyl alcohol, benzaldehyde, benzoic acid, phthalic anhydride and trace amounts of toluene, xylene, and phenol. Although this method manages to achieve high selectivity towards benzoic acid, it needs high temperature and long contact times which are limitations. In addition, kinetics and mechanisms of the oxidation of methylaryl ketones by acid permanganate were studied. (ii) Oxidative cleavage of alkenes and alkynes: The oxidation of alkenes and alkynes by ozonolysis or acidic potassium permanganate (KMnO4/H3O+) breaks the —CH═CH— bond, when a hydrogen atom is attached to each of the alkene carbons in the starting material. In case a hydrogen atom is attached to the carbonyl carbon in the product, the product is an aldehyde which can be rapidly transferred into a carboxylic acid group. If the alkene has no hydrogens attached, the product is a ketone which cannot be easily oxidized further. The alkyne is more highly oxidized than an alkene and the ozonolysis leads to the cleavage which involves the formation of a carboxylic acid groups. For examples, see V. R. Chumbahale et al., Chem. Engi. Res. Design 2005, 83, 75-80; M. P. Nath et al., Aust. J. Chem., 1976, 29, 1939-1945. (iii) Oxidative cleavage of 1,2-diols: Organocatalytic one-pot oxidative cleavage of terminal 1,2-diols to one-carbon-unit-shorter carboxylic acids is catalyzed by 1-Me-AZADO in the presence of a catalytic amount of NaOCl and NaClO2 under mild conditions. Aerobic photo-oxidative cleavage of 1,2-diols yields carboxylic acids using 2-chloroanthraquinone in the presence of photo-irradiation with a high-pressure mercury lamp. (iv) Oxidative cleavage of 1,3-di-carbonyls: Catalytic oxidative cleavage of 1,3-diketones enables the synthesis of the corresponding carboxylic acids, for example, by aerobic photo-oxidation with iodine under irradiation with a high-pressure mercury lamp or by conversion of β-ketoesters and β-diketones using CAN (cerium ammonium nitrate) in CH3CN (Y. Zang et al., J. Org. Chem. 2006, 71, 4516-4520).(2) Hydrolysis Reactions:(a) Hydrolysis of nitriles and amides: Nitriles can be hydrolyzed to carboxylic acids without the isolation of amide intermediate. The carbon skeleton is extended by one carbon atom during this reaction sequence, in which the cyanide anion is a nucleophilic precursor of the carboxyl group. The hydrolysis may be either acid or base-catalyzed, but the latter gives a carboxylate salt as the initial product.(b) Hydrolysis of acid chlorides, esters and anhydrides: N,N-diarylammonium pyrosulfate efficiently catalyzes the hydrolysis of esters under organic solvent-free conditions.(3) Other Methods for Preparations of Carboxylic Acids:(i) Benzilic acid rearrangement of 1,2-diketones: 1,2-Diketones undergo a rearrangement in the presence of strong base to yield α-hydroxycarboxylic acids. The best yields are obtained when the diketones do not have enolizable protons. (ii) Favorskii Reaction of cyclopropanones and α-halo ketones: The rearrangement of cyclopropanones, often obtained as intermediates from the base-catalyzed reaction of α-halo ketones, leads to the formation of carboxylic acids and their derivatives. (iii) Carboxylation of organometallics with CO2: Organometallic intermediate compounds such as Grignard reagents react with carbon dioxide, as an electrophile, usually in Et2O or THF followed by H3O+ work-up. The initial product is a salt of the carboxylic acid, which must then be released by treatment with strong aqueous acid. (iv) Carboxylation of alcohols, esters, ethers or halides with CO: Alcohols, esters, ethers or halides can be converted to a carboxylic acid in the liquid phase with carbon monoxide at temperatures between 50-300° C. and at partial pressures of carbon monoxide 10-1,000 p.s.i.g., in the presence of a catalyst system containing rhodium and a halogen component as active constituents.
Nitrosation of active methylene compounds has been effected by nitrous acid, an inorganic nitrite and an acid, an alkyl nitrite and an inorganic acid or base, nitrosylchloride, nitrosylsulfuric acid, nitrogen trioxide and nitric oxide. However, none of these nitrosating agents is equally effective with all active methylene compounds. U.S. Pat. No. 2,749,358 describes a process for the preparation of oximes by reacting a nitric oxide and a compound containing an active methylene group by temperatures of 50 to 150° C. under pressure in the presence of a variable-valence-metal salt catalyst. Further, it is described that ease and degree of nitrosation depends primarily on the ability of the adjacent electron-attracting groups to promote nitrosation. Moreover, higher temperatures and pressure, longer reaction times and more active catalysts caused oxidation of the oximes formed to acids or oxidized tarry mixtures.